Amylyx Pharmaceuticals Announces First Participant Dosed in the Global Phase 3 ORION Study of AMX0035 in Progressive Supranuclear Palsy (PSP)

CAMBRIDGE, Mass. — Amylyx Pharmaceuticals, Inc. today announced that the first participant has been dosed in ORION, a randomized, double-blind, placebo-controlled Phase 3 clinical trial of AMX0035 (sodium phenylbutyrate [PB] and taurursodiol [TURSO]) for the treatment of progressive supranuclear palsy (PSP). The Phase 3 trial will enroll approximately 600 participants in approximately 100 sites across the United States, Canada, the European Union, the United Kingdom, and Japan, making this the largest PSP clinical trial to date.

“There is a pressing unmet need within the PSP community for new and effective treatment options, as no disease-modifying therapies have been approved for the treatment of the disease,” said Dr. Kristophe Diaz, Executive Director and Chief Science Officer at CurePSP. “We’re looking forward to continuing our collaboration on ORION, recognizing that a united global effort is essential to usher in promising advancements and raise awareness for people living with PSP and their families.”

The primary efficacy endpoint will evaluate change in disease progression from baseline to Week 52 as measured by total score on the 28-item Progressive Supranuclear Palsy Rating Scale (PSPRS), an established and validated endpoint in PSP clinical trials.

Secondary efficacy endpoints are disease progression as measured by a modified 10-item PSPRS score and motor aspects of activities of daily life as measured by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part 2 (MDS-UPDRS Part II). Exploratory outcomes include changes in activities of daily living, cognitive function, quality of life, overall survival, brain regional volumes, fluid biomarkers of neuronal injury/inflammation, and caregiver burden.

Safety and tolerability will be evaluated by assessing the frequency of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs). Participants completing the 52-week randomized, placebo-controlled phase of the trial will have the option to enroll in an Open Label Extension where all participants will receive AMX0035 for up to an additional year. Topline results are anticipated in 2-3 years.

“AMX0035 has a strong scientific rationale in PSP, targeting key upstream pathways in disease pathophysiology including the unfolded protein response and mitochondrial dysfunction. Furthermore, PSP is a tauopathy associated with tau dysfunction, tau aggregation, and widespread neurodegeneration, and AMX0035 has been shown to reduce p-tau in a previous Alzheimer’s disease trial. These components are essential to the pathophysiology of PSP, and we are excited about the strong scientific rationale supporting AMX0035 in PSP,” said Prof. Dr. Günter Höglinger, Director of the Department of Neurology at Ludwig-Maximilians-University (LMU) Hospital, Munich, Germany, and Primary Investigator of the Phase 3 ORION clinical trial.

“Given PSP is a relentlessly progressive disease, it is imperative that we respond to the unmet needs of the community with a sense of urgency. Our current focus is on activating clinical trial sites in all participating regions in order to complete the trial as quickly and efficiently as possible, gearing toward what could potentially be the first therapy for the PSP community,” said Lahar Mehta, MD, Head of Global Clinical Development at Amylyx.

 

About AMX0035 / RELYVRIO®/ ALBRIOZA™ / ALBRIOZA®

AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol (known as ursodoxicoltaurine outside of the U.S.). It is approved as RELYVRIO® to treat amyotrophic lateral sclerosis (ALS) in adults in the U.S. and approved with conditions as ALBRIOZA™ for the treatment of ALS in Canada. AMX0035 is being studied for the potential treatment of other neurodegenerative diseases, and Amylyx is exploring its treatment in other populations and regions. The formulation of RELYVRIO, ALBRIOZA, and AMX0035 is identical.

 

About the ORION Trial

The Phase 3 ORION trial (NCT06122662) is a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial designed to assess the efficacy, safety, and tolerability of AMX0035 compared to placebo in people living with progressive supranuclear palsy (PSP). Approximately 600 participants will be enrolled across the United States, Canada, the European Union, the United Kingdom, and Japan. The ORION Phase 3 trial was designed and planned in collaboration with key global academic leaders, people living with PSP and their caregivers, and industry advocacy organizations.

 

About Amylyx Pharmaceuticals

Amylyx Pharmaceuticals, Inc. is committed to supporting and creating more moments for the neurodegenerative community through the discovery and development of innovative new treatments. Amylyx is headquartered in Cambridge, Massachusetts and has operations in Canada, EMEA, and Japan.

 

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